Kimihiro Okubo

Nippon Medical School, Sendai, Kagoshima-ken, Japan

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Publications (55)58.58 Total impact

  • Article: Severity Assessment of Japanese Cedar Pollinosis Using the Practical Guideline for the Management of Allergic Rhinitis in Japan and the Allergic Rhinitis and its Impact on Asthma Guideline.
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    ABSTRACT: Background: This study intended to assess the severity of Japanese cedar pollinosis using the Practical Guideline for the Management of Allergic Rhinitis in Japan (PG-MARJ) and the Allergic Rhinitis and its Impact on Asthma (ARIA) Guideline. Methods: An Internet questionnaire survey of patients with pollinosis was conducted in mid-May 2011 and responses were obtained from 3382 individuals who had potential symptoms of Japanese cedar pollinosis from February to early May 2011 and who had experienced such symptoms for at least two pollen seasons. Results: According to PG-MARJ, 23.5% of the respondents had severest rhinitis, 29.4% severe rhinitis, 31.3% moderate rhinitis, 13.8% mild rhinitis and 2.0% asymptomatic rhinitis. According to ARIA, 67.2% of them had moderate/severe persistent rhinitis, 23.8% moderate/severe intermittent rhinitis, 4.4% mild persistent rhinitis and 4.6% mild intermittent rhinitis. Conclusions: Moderate to severe rhinitis was diagnosed in more than 80% of the respondents according to PG-MARJ, while moderate/severe rhinitis was diagnosed in more than 90% of the respondents according to ARIA. Most of the respondents suffered relatively severe pollinosis. More than 80% of the respondents had all the three major symptoms (i.e., sneezing, rhinorrhea and nasal blockage). Disagreement in the severity assessment between the two guidelines was noted in approximately 20% of the respondents.
    Allergology International 02/2013;
  • Article: The Necessity of Simple X-ray Examination: A Case Report of Button Battery Migration Into the Nasal Cavity.
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    ABSTRACT: Since the discovery of button battery, it has been widely applied in various electric devices. However, the button battery has a potential risk as a foreign body in the nasopharyngeal field. Thus, there is a need for early diagnosis and removal of these batteries. We experienced a case of foreign body in the nasal cavity. A battery was lost around a 2-year-old patient. He visited a local pediatric clinic. X-ray examination of the neck, chest. and abdomen showed no sign of a foreign body. He subsequently exhibited left cheek swelling and came to our clinic. X-ray examination of head revealed a metallic foreign body in the left nasal cavity. The foreign body was approached using an endoscope under general anesthesia. The nasal cavity was filled with necrotic tissue. We removed the foreign body using forceps. After surgery, perforation of nasal cavity was identified. The button battery was a potential risk because it contained toxic substances, could release an electrical current, and exerted direct pressure on the surrounding tissues. Surgical removal of button battery is the treatment of first choice. As for late complications, saddle nose is reported. Our patient would receive nasoplastic surgery around the age of 18 years. In summary, our patient's nose was not initially examined using x-ray study. It is very important to keep in mind the possibility of a nasal foreign body, not only for ear, nose, and throat doctors but also for pediatricians.
    Pediatric emergency care 02/2013; 29(2):209-11. · 0.92 Impact Factor
  • Article: Noninvasive biological evaluation of response to pranlukast treatment in pediatric patients with Japanese cedar pollinosis.
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    ABSTRACT: Pranlukast (PLK) is a cysteinyl leukotriene receptor 1 antagonist approved for the treatment of bronchial asthma and allergic rhinitis in Japan. We previously reported that PLK dry syrup (DS) improved the total nasal symptom score, as well as sneezing, nasal discharge, and nasal obstruction scores over placebo. We investigated the efficacy of PLK DS with a noninvasive method in 10- to 15-year-old children with Japanese cedar (JC) pollinosis challenged with pollen allergen using an artificial exposure chamber (OHIO Chamber). Levels of eosinophil cationic protein (ECP) in nasal secretions, nasal obstruction score, and the relationship with nasal obstruction scores were analyzed. The estimated difference of means in ECP levels (PLK DS - placebo) was -22.9 micrograms (95% CI, -45.2 to -0.5), suggesting PLK DS reduced ECP significantly when compared with placebo (p = 0.0454). The difference in the least square means for nasal obstruction between the PLK DS and placebo was -0.25 (95% CI, -0.36 to -0.14) with a value of p < 0.0001. In addition, a statistically significant, although weak, positive correlation between the nasal obstruction score and nasal ECP levels was observed with placebo treatment (correlation coefficient = 0.2394; p = 0.0428). Moreover, the inhibition rate of nasal ECP with PLK DS relative to placebo was statistically significant, although weak, positively correlated with the inhibition rate of nasal obstruction (correlation coefficient = 0.3373; p = 0.0219). PLK DS significantly decreases nasal ECP levels and nasal obstruction score compared with placebo in children with JC pollinosis challenged with pollen allergen. Suppression of mucosal eosinophilic inflammation is one of the pathways by which PLK DS improves pollinosis-induced nasal obstruction.
    Allergy and Asthma Proceedings 11/2012; 33(6):459-66. · 2.17 Impact Factor
  • Article: Cochlin expression in the rat perilymph during postnatal development.
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    ABSTRACT: Abstract Conclusions: The changes in the cochlin isoforms in the perilymph may provide important insights to the understanding of cochlin function and the pathogenesis of related inner ear diseases. Objectives: Cochlin is involved in various pathologies of the inner ear. Altered levels of cochlin isoforms in developing inner ear tissue were reported previously. The purpose of this study was to elucidate the cochlin isoform expression in the perilymph of rats during postnatal development in relation to Coch gene mRNA expression. Methods: We studied the cochlin isoforms in the rat perilymph during postnatal development by Western blot analysis. Real-time PCR was also performed to elucidate the expression level of Coch mRNA in the developing inner ear of rats. Results: Western blot analysis showed that the expression of p63s in the perilymph was highest on the 12th day after birth (DAB12), the earliest age at which we could identify the perilymphatic space microscopically, and it decreased gradually as the cochlea developed. On the other hand, the expression of Cochlin-tomoprotein (CTP)was lowest on DAB12 and increased gradually up to DAB24. COCH mRNA was detected from DAB3 and gradually increased to DAB15, and then gradually decreased to DAB70.
    Acta oto-laryngologica 09/2012; 132(11):1134-9. · 0.98 Impact Factor
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    Article: Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.
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    ABSTRACT: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.
    Allergy, asthma & immunology research 07/2012; 4(4):231-9. · 1.91 Impact Factor
  • Article: Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline.
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    ABSTRACT: Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials.
    Auris, nasus, larynx 03/2012; 39(6):553-6. · 0.58 Impact Factor
  • Article: Acoustic stimulation promotes DNA fragmentation in the Guinea pig cochlea.
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    ABSTRACT: Apoptosis can be described as programmed cell death. Apoptosis regulates cell turnover and is involved in various pathological conditions. The characteristic features of apoptosis are shrinkage of the cell body, chromatin condensation, and nucleic acid fragmentation. During apoptosis, double-stranded DNA is broken down into single-stranded DNA (ssDNA) by proteases. Acoustic trauma is commonly encountered in otorhinolaryngology clinics. Intense noise can cause inner ear damage, such as hearing disturbance, tinnitus, ear fullness, and decreased speech discrimination. In this study, we used immunohistochemical and electrophysiological methods to examine the fragmentation of DNA in the cochleas of guinea pigs that had been exposed to intense noise. Twenty-four guinea pigs weighing 250 to 350 g were used. The animals were divided into 4 groups: (I) a control group (n=6), (II) a group that was exposed to noise for 2 hours (n=6), (III) a group that was exposed to noise for 5 hours (n=6), and (IV) a group that was exposed to noise for 20 hours. The stimulus was a pure tone delivered at a frequency of 2 kHz. The sound pressure level was 120 dBSPL. No threshold shifts were apparent in group I. Group II showed a significant elevation of the hearing threshold (ANOVA, p<0.05(*)). The ABR threshold level was also significantly elevated immediately after the acoustic stimulation in groups III and IV (ANOVA, p<0.01(**)). In groups I, II, and IV, the lateral wall of the ear did not show immunoreactivity to ssDNA but did in group III. No immunoreactivity was apparent in the organ of Corti in group I or II. However, the supporting cells and outer hair cells in groups III and IV showed reactions for ssDNA. The fine structure of the organ of Corti had been destroyed in group IV. The lateral wall showed immunoreactivity for ssDNA only in group III, whereas the organ of Corti showed reactions for ssDNA in groups III and IV. Our study suggests that apoptotic changes occur in patients that suffer acoustic trauma. Once the apoptotic pathway has started, it is irreversible. Thus, early diagnosis and treatment are necessary. Earplugs should also be worn at rock concerts.
    Journal of Nippon Medical School 01/2012; 79(5):349-56.
  • Article: Solitary fibrous tumor arising from the superior nasal turbinate: a case report.
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    ABSTRACT: Solitary fibrous tumor is a rare neoplasm, which was first described as a primary spindle-cell tumor of the pleura, is a type of mesenchymal tumor. Although the majority of these tumors originate in the pleura, they can also derive from extrapleural sites, such as the liver, lung, abdomen, and extremities. We report a rare case of a nasal solitary fibrous tumor that originated from the nasal superior turbinate. The tumor, measuring 45 × 25 × 10 mm, was in the right nasal cavity. We successfully removed the tumor in one piece through endonasal endoscopic surgery. The tumor had spindle-shaped cells within a collagenous stroma and was positive for CD34. There has been no evidence of tumor recurrence in the 14 months following surgery.
    Journal of Nippon Medical School 01/2012; 79(5):373-6.
  • Article: Inducible nitric oxide synthase participates in cochlear damage after acoustic stimulation in Guinea pigs.
    Shunta Inai, Ken-ichi Watanabe, Kimihiro Okubo
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    ABSTRACT: Inducible nitric oxide synthase (iNOS/NOS II) mediates cytotoxicity under pathological stimulation. The purpose of this study was to examine whether the blockade of NOS activity leads to a decrease in cochlear damage after intense acoustic stimulation. Guinea pigs were divided into 4 groups: (1) a noise group, (2) a NOS inhibitor (N<sup>G</sup>-nitro-L-arginine methyl ester [L-NAME]) + noise group (L-NAME/noise group), (3) an L-NAME group, and (4) a control group. Stimuli involved a pure tone at a frequency of 2 kHz for 5 hours. The sound pressure level was 120 dBSPL. In the L-NAME/noise group, 50 mg/kg body weight of L-NAME was injected 1 hour before acoustic stimulation. In the control group and the L-NAME group, acoustic stimulation was not performed. In the L-NAME group, the same dose of L-NAME was injected intraperitoneally. In the control group, only physiological saline was injected. Auditory brainstem responses (ABRs) were recorded before and immediately, 1 day, and 7 days after acoustic stimulation. The ABR threshold was significantly higher immediately after acoustic stimulation in both the noise group and the L-NAME/noise group. One day after acoustic stimulation, the threshold shift was decreased in the noise group. The threshold shift was still present 7 days after acoustic stimulation but was significantly lower in the L-NAME/noise group than in the noise group. In the L-NAME group and the control group, threshold shifts were not apparent. The lateral wall, the organ of Corti, and the spiral ganglion cells of the cochlea in both the L-NAME group and the control group did not display immunoreactivity for iNOS at any time. Immunoreactivity for iNOS was found in the lateral wall, the supporting cells (Hensen's cells, Deiters' cells, and pillar cells), and the spiral ganglion cells in both the noise group and the L-NAME/noise group. These immunoreactivities for iNOS were detected immediately, 1 day, and 7 days after acoustic stimulation. Immunoreactivity decreased over time in the stria vascularis, the organ of Corti, and the spiral ganglion cells in the noise group. The same phenomenon was observed in the L-NAME/noise group. In conclusion, iNOS was detected in cochlea damaged by acoustic stimulation. A NOS inhibitor (L-NAME) reduced the elevation of hearing thresholds. Our results suggest that the expression of iNOS participates in the pathogenesis of cochlear damage caused by acoustic trauma.
    Journal of Nippon Medical School 01/2012; 79(2):121-8.
  • Article: Pranlukast dry syrup inhibits symptoms of Japanese cedar pollinosis in children using OHIO Chamber.
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    ABSTRACT: Pranlukast (PLK) is a leukotriene receptor antagonist (LTRA) that has been approved for treatment of asthma in patients of all ages and allergic rhinitis (AR) in adults but not for AR in children in Japan. This randomized, double-blind, placebo-controlled, crossover study used an artificial exposure chamber (OHIO Chamber) to investigate the efficacy and safety of PLK in children from 10 to 15 years old with seasonal AR (SAR) due to Japanese cedar (JC) pollen. Eighty-four subjects were enrolled and randomized to the treatment arm and 74 were included in the per protocol set. Subjects received either PLK dry syrup (DS) or placebo for 1 week. They were challenged with JC pollen in the OHIO Chamber for 3 hours. Total nasal symptom scores (TNSSs) were recorded every 30 minutes during the exposure. PLK DS treatment suppressed the TNSS changes from baseline significantly when compared with placebo. The difference in the least square means in TNSS between the PLK DS-treated group and placebo group was -0.37 (95% CI, -0.54, -0.20) with a value of p < 0.0001, showing that PLK DS significantly suppressed the nasal symptoms. Regarding specific nasal symptoms, PLK DS significantly suppressed sneezing, nasal discharge, and nasal obstruction. The effect of PLK DS on nasal obstruction was most prominent, with significant improvement relative to placebo beginning 60 minutes after the start of exposure. No serious adverse events were reported during the study. In this study, PLK DS is effective and safe for treatment in children with SAR.
    Allergy and Asthma Proceedings 01/2012; 33(1):102-9. · 2.17 Impact Factor
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    Article: Efficacy of epinastine hydrochloride for antigen-provoked nasal symptoms in subjects with orchard grass pollinosis.
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    ABSTRACT: Among the gramineae species, orchard grass is a typical causative pollen that provokes seasonal rhinitis. The purpose of this study was to examine the protective efficacy of epinastine hydrochloride for signs and symptoms caused by repeated nasal provocation with discs containing orchard grass pollen. A single-dose, placebo-controlled, double-blind, crossover clinical study was conducted in subjects with orchard grass pollinosis. The pollen challenge was conducted with the use of provocation discs containing orchard grass pollen. Epinastine hydrochloride suppressed nasal symptoms caused by nasal provocation tests using orchard grass pollen discs. Among the nasal symptoms, the number of sneezing was significantly inhibited 30 minutes and 60 minutes after the administration of epinastine hydrochloride, as compared with placebo. There were no adverse reactions to the study drugs. Our results suggest that nasal provocation tests with discs containing orchard grass pollen is a useful method for evaluating the onset of action of antiallergic drugs. As compared with placebo, epinastine hydrochloride decreased early-phase sneezing and the total nasal symptom score after repeated nasal provocations with orchard grass pollen discs.
    Allergology International 12/2011; 60(1):69-77.
  • Article: Surgical management of tongue cancer during pregnancy.
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    ABSTRACT: There are ethical dilemmas in managing head and neck cancers during pregnancy. Diagnostic and treatment modalities need to be carefully determined. We herein describe 3 cases of tongue cancer during pregnancy. The details of the management would contribute to the daily practices for head and neck cancers. All three patients were Japanese female patients, two of them were 29 years old and one was 26 years old. All patients were admitted to the Nippon Medical School Hospital during pregnancy, complaining of oral pain and/or discomfort. Case 1 was diagnosed as tongue cancer stage T3N0M0, however, the tumor was superficial and controllable by partial glossectomy. Case 2 was stage T2N0M0 with deep invasion with ulcer, and the hemi-glossectomy with neck dissection and the reconstruction was thought to be the standard modality. However, she underwent partial glossectomy in order to reduce the stress of the fetus. Case 3 could not be diagnosed on admission by biopsy and she underwent partial glossectomy after delivery. In case 3, the pathological diagnosis was pT1 tongue cancer. In case 1 and case 3, the patient and baby were healthy. In case 2, however, the patient died of recurrence at the primary site. In decision making of the strategy, the most important factors are not only oncological evaluation but also ethical and emotional factors.
    Auris, nasus, larynx 08/2011; 39(4):428-30. · 0.58 Impact Factor
  • Article: Delay of onset of symptoms of Japanese cedar pollinosis by treatment with a leukotriene receptor antagonist.
    Minoru Gotoh, Hidenori Suzuki, Kimihiro Okubo
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    ABSTRACT: Leukotriene receptor antagonists (LTRAs) are effective for prophylactic treatment of pollinosis based on studies showing that administration of LTRAs prior to or at the start of the pollen season reduces symptoms and QOL disturbance at the peak of pollen dispersal. Two goals of prophylactic treatment of pollinosis are use of fewer types of drugs and delay of onset of symptoms and impairement of QOL. Therefore, this study was performed to determine if pranlukast, a LTRA, met these goals in treatment of pollinosis. Pranlukast or placebo was administered to patients who visited our hospital immediately before the start of Japanese cedar pollen dispersal. The study was performed for 4 weeks as a double blind randomized trial. Subsequently, all patients were given pranlukast for a further 4 weeks from the peak until the end of pollen dispersal. The incidence of symptoms and use of concomitant drugs were investigated from daily nasal allergy records kept by patients. QOL was evaluated using the JRQLQ questionnaire. In the double blind period of the study, the percentage of patients who used concomitant drugs for nasal symptoms was significantly lower in the pranlukast group compared to the placebo group. Development of nasal symptoms (sneezing, runny nose and nasal congestion) and disturbance of daily activities were significantly delayed in the pranlukast group. No serious adverse reactions occurred in the pranlukast group and no patient withdrew from treatment with pranlukast. Pranlukast is effective for prophylactic treatment of pollinosis.
    Allergology International 07/2011; 60(4):483-9.
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    Article: Increased expression and role of thymic stromal lymphopoietin in nasal polyposis.
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    ABSTRACT: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.
    Allergy, asthma & immunology research 07/2011; 3(3):186-93. · 1.91 Impact Factor
  • Article: Cochlin-tomoprotein (CTP) detection test identifies traumatic perilymphatic fistula due to penetrating middle ear injury.
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    ABSTRACT: The cochlin-tomoprotein (CTP) detection test can be used to make a definite, objective diagnosis of traumatic perilymphatic fistula (PLF), and therefore offers valuable information on patient selection for surgical treatment. Penetrating middle ear injury can cause traumatic PLF, which is a surgically treatable otologic emergency. Recently, we have reported on CTP, a novel perilymph-specific protein. The purpose of this study was to determine if the CTP detection test is useful for the diagnosis of traumatic PLF. This was a prospective study of CTP detection in penetrating middle ear injury cases with tympanic membrane perforation and hearing loss. A total of seven individuals were included in this study. CTP was detected in three of four cases with posterosuperior quadrant perforation of the tympanic membrane. In one of these three cases, even though the high resolution CT scan was not suggestive of PLF and the perilymph leakage could not be visualized intraoperatively, the CTP detection test was able to detect PLF. In two cases, the preoperative positive test results enabled us to make a diagnosis of PLF and a decision for surgical treatment. CTP was not detected in the cases with anterior or inferior tympanic membrane perforation.
    Acta oto-laryngologica 06/2011; 131(9):937-44. · 0.98 Impact Factor
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    Article: Japanese guideline for allergic rhinitis.
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    ABSTRACT: Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 6th edition was published in 2009, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2009. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women.
    Allergology International 03/2011; 60(2):171-89.
  • Article: A randomized, double-blind, placebo-controlled study of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis.
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    ABSTRACT: Self-care with ten-cha is the most common complementary alternative medicine for allergic rhinitis in Japan, but evidence for an actual therapeutic effect is lacking. The purpose of the study was to investigate the effect of ten-cha (Rubus suavissimus) on house dust mite allergic rhinitis. The study was performed in the otolaryngology departments of 5 facilities (Chiba University, Kagoshima University, Fukui University, Okayama University, and Nippon Medical School) from July to December 2009. A randomized double-blind study was performed with central enrollment and allocation. The subjects ingested 400mg of ten-cha extract or placebo (3 capsules/day) daily for 4 weeks as a food intervention. The number of subjects was chosen with anticipation of an effect equivalent to that of mast cell-stabilizing drugs. A nasal allergy diary-based symptom score and a QOL score were used for evaluation. The ten-cha and placebo groups included 47 and 42 subjects, respectively. The improvement rates for sneeze, nasal discharge, nasal obstruction, and symptom scores were greater in the ten-cha group than in the placebo group throughout the intervention period, and the effect tended to increase with time in the ten-cha group. However, the differences between the groups were not significant. QOL was not significantly improved in either group. Ingestion of ten-cha had an effect on allergic rhinitis, but the effect of Ten-Cha was limited and did not differ significantly from placebo. These results suggest that ten-cha does not exhibit an effect equivalent to mast cell-stabilizing drugs at the dose used in this study.
    Auris, nasus, larynx 01/2011; 38(5):600-7. · 0.58 Impact Factor
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    Article: Three cases of carcinoma of the hypopharynx developing as metachronous second primary cancers after total laryngectomy with radiotherapy for carcinoma of the larynx.
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    ABSTRACT: We describe 3 cases of metachronous hypopharyngeal cancer developing after laryngeal cancer had been treated with both radiotherapy and total laryngectomy. All 3 patients were men, 2 were 89 years old, and 1 was 65 years old. All patients had undergone total laryngectomy and radiotherapy for cancer for the glottis more than 20 years earlier. All patients underwent total hypopharyngectomy with jejunal free flap reconstruction. Surgery was complicated by scars from previous cancer treatment, and highly sophisticated surgical skills are needed, especially for preparing the recipient vessels. The postoperative period was largely uneventful and without fatal complications, however, 2 of the 3 patients died of distant metastasis 22 months and 31 months after surgery.
    Journal of Nippon Medical School 01/2011; 78(4):261-6.
  • Article: Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis.
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    ABSTRACT: Allergic rhinitis is a global health problem that causes major illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. However, the precise mechanism underlying allergen-SIT is not well understood. The aim of the current study was to identify protein expression signatures reflective of allergen-SIT-more specifically, sublingual immunotherapy (SLIT). Serum was taken twice from patients with seasonal allergic rhinitis caused by Japanese cedar: once before the pollen season and once during the season. A total of 25 patients was randomly categorized into a placebo-treated group and an active-treatment group. Their serum protein profiles were analyzed by 2-dimensional electrophoresis. Sixteen proteins were found to be differentially expressed during the pollen season. Among the differentially expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA-IV), and transthyretin were significantly increased in SLIT-treated patients but not in placebo-treated patients. Among these proteins, the serum levels of apoA-IV correlated with the clinical symptom-medication scores (r = -0.635; P < .05) and with quality of life scores (r = -0.516; P < .05) in the case of SLIT-treated patients. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium (P < .01). Our data will increase the understanding of the mechanism of SLIT and may provide novel insights into the treatment of allergic rhinitis.
    The Journal of allergy and clinical immunology 12/2010; 126(6):1163-9.e5. · 9.17 Impact Factor
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    Article: Allergen immunotherapy for allergic rhinitis.
    Kimihiro Okubo, Minoru Gotoh
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    ABSTRACT: Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the 2 forms of desensitization for allergic diseases which are used internationally. Despite the lack of sufficient evidence of the mechanism, SCIT has been used in Japan. When SCIT is performed appropriately, it is effective for allergic rhinitis, as supported by high-level evidence, including the results of meta-analysis. However, its use in Japan has not become widespread due to various problems, including the risk of anaphylaxis. Therefore, attention is being focused on SLIT because it is easier to perform but may be similarly effective and has been extensively discussed and evaluated internationally. Comparison of SCIT and SLIT can only be done with some allergen, which has also been discussed extenesively. Many patients and physicians would welcome the use of SLIT in Japan, and its first use against pollinosis due to Japanese cedar pollen is planned for 2014.
    Journal of Nippon Medical School 12/2010; 77(6):285-9.

Institutions

  • 2003–2013
    • Nippon Medical School
      • Department of Otolaryngology
      Sendai, Kagoshima-ken, Japan
  • 2009–2011
    • Chiba University
      • Department of Otorhinolaryngology, Head and Neck Surgery
      Chiba-shi, Chiba-ken, Japan
    • Kitasato University
      Tokyo, Tokyo-to, Japan
    • Tokyo Medical University
      • Department of Otorhinolaryngology
      Tokyo, Tokyo-to, Japan